Recent Regulatory Scenario of Nitrosamines Impurities in Regulated Market US, Europe and Canada
Abstract
Unexpected finding of cancer causing, DNA damaging impurities called nitrosamine impurities which are mostly likely to present in structures containing nitroso group as per EMA and also according to ICH M7 is a member of “cohort of concern “class of high potency mutagenic carcinogens. In year 2018 it was first detected in sartans by USFDA after that it found in found in antacid like nizatidine, ranitidine and in anti-diabetic drugs like metformin, pioglitazone. There are nearly more fifteen types of impurities detected in products like NDMA, NDEA, EIPNA, NMBA, NDBA, and MeNP. Thousands of batches were recalled in countries like USA, Europe and all around world. Regulatory bodies of like USFDA, EMA and Health Canada has published stringent guidelines and documents to control carcinogenic impurities and given timelines for submission of risk assessment and confirmatory test and submission of other documents if change in process to mitigate its level and suggested changes in manufacturing process like change in ROS ,Control strategy etc. Along with the Q&A, roots cause for presence of impurities .Immediate submission of the amount of Nitrosamine impurities when detected in product and if negligible amount is present no need to submit report.
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References
https://www.fda.gov/media/141720/download
2. Nitrosamine impurities in human medicinal products [Internet]. European Medicines Agency; 2020 Jun [cited 2023 Jan 01]. Available from:
https://www.ema.europa.eu/en/documents/referral/nitrosamines-emea-h-a53-1490-assessment-report_en.pdf
3. The EDQM’s Response to Nitrosamine Contamination [Internet]. The European Directorate for the Quality of Medicines & HealthCare [cited 2023 Jan 01]. Available from:
https://www.edqm.eu/en/edqms-response-nitrosamine-contamination
4. WHO Information Note: Update on Nitrosamine impurities [Internet]. World Health Organization; 2020 Apr [cited 2023 Jan 01]. Available from:
https://www.who.int/docs/default-source/substandard-and-falsified/informationnote-nitrosamine-impurities-april2020.pdf
5. European Medicines Agency. Assessment report: Nitrosamine impurities in human medicinal products. 2020;5(June):1-90.
6. Byrn, S., & Stowell, J. Impurities in Drug Substances and Drug Products. Validation of Active Pharmaceutical Ingredients, Second Edition. 2001 Dec;2(1):271–292. https://doi.org/10.1201/b14415-10
7. Lijinsky W. Health Problem with Nitrites Associated and Nitrosamine. Ambio. JSTOR. 1976; 5(2): 67-72
http://www.jstor.org/stable/4312174.
8. Karuna, K. & Balamuralidhar, V. Nitrosamine impurities: The European policy review. Drug Invention Today. 2020 Jun;13(6):1–2.
http://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=09757619&AN=143462594&h=kHiRCJPOcDe3X4BUk3yBp0A%2BCo98WUPXkzm%2FETCiUGqwWTsTmoxxMG47zeipx5%2FJ6y6c7jnA8HuTWevf4VgVlg%3D%3D&crl=c
9. Iram M. From Valsartan to Ranitidine: The Story of Nitrosamines So Far. Indian Journal of Pharmacy Practice.2020;13(1):01–02
https://doi.org/10.5530/ijopp.13.1.1
10. European Medicines Agency. Lessons learnt from presence of N-nitrosamine impurities in sartan medicines. [Internet]. European Medicines Agency; 2020 [cited 2023 Jan 08]. Available from:
https://www.ema.europa.eu/en/documents/report/lessons-learnt-presence-n-nitrosamine-impurities-sartan-medicines_en.pdf
11. Request To Evaluate the Risk of the Presence of N -Nitrosamine Impurities in Human [Internet]. European Medicines Agency; 2021 Apr 12 [cited 2023 Jan 09]. Available from:
https://www.ema.europa.eu/en/human-regulatory/post-authorisation/referral-procedures/nitrosamine-impurities
12. Leistner, A., Haerling, S., Kreher, J. D., Becker, I., Jung, D., & Holzgrabe, U. Risk assessment report of potential impurities in cetirizine dihydrochloride. Journal of Pharmaceutical and Biomedical Analysis. 2020;189: 113425.
https://doi.org/10.1016/j.jpba.2020.113425
13. Dobariya U, Chauhan N, Patel H, Pardeshi N. Nitrosamine Impurities: Origin, Control and Regulatory Recommendations. Int J Drug Reg Affairs [Internet]. 2021 Jun.17 [cited 2023 Jan. 26];9(2):77-0. Available from:
https://ijdra.com/index.php/journal/article/view/472
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